Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

Ishida,Hisashi; Iguchi,Akihiro; Aoe,Michinori; Nishiuchi,Ritsuo; Matsubara,Takehiro; Keino,Dai; Sanada,Masashi; Shimada,Akira

doi:10.3892/br.2020.1353

Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

Authors:
- Hisashi Ishida
- Akihiro Iguchi
- Michinori Aoe
- Ritsuo Nishiuchi
- Takehiro Matsubara
- Dai Keino
- Masashi Sanada
- Akira Shimada
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Affiliations: Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital, Okayama 700‑8558, Japan, Department of Pediatrics, Hokkaido University Hospital, Sapporo, Hokkaido 060‑8648, Japan, Division of Medical Support, Okayama University Hospital, Okayama 700‑8558, Japan, Department of Pediatrics, Kochi Health Sciences Center, Kochi 781‑8555, Japan, Division of Biobank, Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama 700‑8558, Japan, Department of Pediatrics, St. Marianna University School of Medicine Hospital, Kawasaki, Kanagawa 216‑8511, Japan, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460‑0001, Japan
Published online on: August 28, 2020 https://doi.org/10.3892/br.2020.1353
Article Number: 46
Copyright: © Ishida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30‑40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next‑generation sequencing (NGS) of >150 cancer‑related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3‑ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel‑based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel‑based NGS approach into the clinical setting may allow for a patient‑oriented strategy of precision treatment for childhood AML.

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